It is proposed to use mice homozygous for the iv gene as an animal model of human situs inversus viscerum and associated congenital heart malformations. Using this model the morphogenetic mechanisms leading to situs inversus-related heart malformations will be investigated. Work done in this laboratory has already established that iv/iv mice have a high incidence (about 25%) of severe heart malformations similar to those found in human patients with situs inversus. The effect of genetic background on the incidence and kinds of heart malformation is being determined by placing the iv gene on 7 different inbred strains of mice and on 2 heterogeneous backgrounds. In the coming year the morphogenesis of the heart malformations will be investigated by examination of embryonic hearts in various stages of development using serial sections and also scanning electron microscopy. Intact embryos and hearts will be cultured to see if the steps leading to malformation can be observed in the living heart. Standard methods of culturing organs and embryos will be used.